Structure-based identification of galectin-1 selective modulators in dietary food polyphenols : a pharmacoinformatics approach

In this study, a set of dietary polyphenols was comprehensively studied for the selective identification of the potential inhibitors/modulators for galectin-1. Galectin-1 is a potent prognostic indicator of tumor progression and a highly regarded therapeutic target for various pathological conditions. This indicator is composed of a highly conserved carbohydrate recognition domain (CRD) that accounts for the binding affinity of β-galactosides. Although some small molecules have been identified as galectin-1 inhibitors/modulators, there are limited studies on the identification of novel compounds against this attractive therapeutic target. The extensive computational techniques include potential drug binding site recognition on galectin-1, binding affinity predictions of ~ 500 polyphenols, molecular docking, and dynamic simulations of galectin-1 with selective dietary polyphenol modulators, followed by the estimation of binding free energy for the identification of dietary polyphenol-based galectin-1 modulators. Initially, a deep neural network-based algorithm was utilized for the prediction of the druggable binding site and binding affinity. Thereafter, the intermolecular interactions of the polyphenol compounds with galectin-1 were critically explored through the extra-precision docking technique. Further, the stability of the interaction was evaluated through the conventional atomistic 100 ns dynamic simulation study. The docking analyses indicated the high interaction affinity of different amino acids at the CRD region of galectin-1 with the proposed five polyphenols. Strong and consistent interaction stability was suggested from the simulation trajectories of the selected dietary polyphenol under the dynamic conditions. Also, the conserved residue (His44, Asn46, Arg48, Val59, Asn61, Trp68, Glu71, and Arg73) associations suggest high affinity and selectivity of polyphenols toward galectin-1 protein.The Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, through the Research Groups Program Grant No. (RGP-1440–0021).https://link.springer.com/journal/11030hj2023Chemical Patholog

Pharmacoinformatics-based identification of anti-bacterial catalase-peroxidase enzyme inhibitors

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the present age, due to the rapid increase in antibiotic resistance worldwide, TB has become a major threat to human life. Regardless of significant efforts have been inclined to improve the healthcare systems for improving diagnosis, treatment, and anticipatory measures controlling TB is challenging. To date, there are no such therapeutic chemical agents available to fight or control the bacterial drug-resistance. The catalase-peroxidase enzyme (katG) which encoded by the katG gene of Mtb is most frequently getting mutated and hence promotes Isoniazid resistance by diminishing the normal activity of katG enzyme. In the current study, an effort has been intended to find novel and therapeutically active antibacterial chemical compounds through pharmacoinformatics methodologies. Initially, the five mutant katG were generated by making mutation of Ser315 by Thr, Ile, Arg, Asn, and Gly followed by structural optimizations. About eight thousand small molecules were collected from the Asinex antibacterial library. All molecules were docked to active site of five mutant katG and wild type katG. To narrow down the chemical space several criteria were imposed including, screening for highest binding affinity towards katG proteins, compounds satisfying various criterion of drug-likeliness properties like Lipinski’s rule of five (RO5), Veber’s rule, absorption, distribution, metabolism, and excretion (ADME) profile, and synthetic accessibility. Finally, five molecules were found to be important antibacterial katG inhibitors. All the analyzed parameters suggested that selected molecules are promising in nature. Binding interactions analysis revealed that proposed molecules are efficient enough to form a number of strong binding interactions with katG proteins. Dynamic behavior of the proposed molecules with katG protein was evaluated through 100 ns molecular dynamics (MD) simulation study. Parameters calculated from the MD simulation trajectories adjudged that all molecules can form stable complexes with katG. High binding free energy of all proposed molecules definitely suggested strong affection towards the katG. Hence, it can be concluded that proposed molecules might be used as antibacterial chemical component subjected to experimental validation.The Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia through the Fast-track Research Funding Program.https://www.elsevier.com/locate/cbac2020-12-01hj2019Chemical Patholog

Validation of low dosages of γ-radiation and their effect on red beetle mortality, storability characteristics, and nutritional value of sorghum (Sorghum bicolor L. Moench) grain

This research was undertaken to validate the low dosages of γ-radiation of sorghum to examine the efficiency of gamma irradiation doses in quality attributes and storability of sorghum grain. Infested sorghum grains with the red flour beetle at the adult stage were irradiated at 0.25, 0.5, 0.75, 1.0, and 2.0 kGy emitted by 60CO. Subsequently, the mortality rate of the red flour beetle as affected by gamma doses was estimated and the storability characteristics and nutritional value of sorghum grains were measured. Eventually, the Partial Least Squares regression (PLS) analysis was executed to confirm the optimum dose of gamma which eliminate the red flour beetle and enhanced the grain quality. Results provide that the storability characteristics were enhanced after treatments. However, the changes in the germination rate of the grains were not different significantly after radiation. On the other hand, the radiation process enhanced sorghum grins' nutritional quality. Both tannins and phytic acid content dropped significantly and the digestibility and solubility of protein were gradually incremented in the grains. The PLS results indicated that using 1 and 2 kGy reflect the utmost effective dosage for sorghum. It can be concluded that this method is a potent rapid and operative preservation process to the alternate smoking chemical procedure for improving sorghum’s nutritional and functional quality and prolong its shelf life. Possibility of providing effective and rapid quarantine security as an alternative to chemical fumigation protocol to extend shelf life and enhance the nutritional and functional quality of sorghum